GSK starts combination melanoma trials

Phase III studies could see limitations of current therapies overcome

GlaxoSmithKline (GSK) has started phase III trials of a combination therapy for melanoma which could overcome the limitations of current therapies for the disease.

The therapy will combine GSK's BRAF inhibitor dabrafenib with trametanib, a MEK inhibitor, and is designed to counter the resistance that has been observed with BRAF inhibitors used to treat melanoma.

GSK will run two trials in the phase III programme. The first will examine whether dabrafenib/trametanib is superior to dabrafenib alone in patients with BRAF-positive metastatic cutaneous melanoma, while the second will be a head-to-head assessment of the combination versus Roche/Daiichi's Zelboraf (vemurafenib), the only BRAF inhibitor to have reached the market to date.

Zelboraf has been hailed as a breakthrough in melanoma, racking up around $30m in its first few weeks on the US market after FDA approval in August 2011, and analysts have predicted it could reach peak annual sales of $1bn-$1.5bn.

However, several mechanisms of resistance to BRAF inhibition have been uncovered, and in the case of Zelboraf oncologists cannot simply give more of the drug to overcome resistance because the dose approved is the maximum that is tolerated.

"While recent clinical findings with BRAF inhibitors in melanoma have shown significant improvement over chemotherapy, eventually tumours become resistant to these inhibitors leading to disease relapse," said Dr Rafael Amado, head of oncology R&D at GSK.

"Recent scientific advances have led us to the hypothesis that the combination of BRAF and MEK inhibitors may delay resistance," Amado added.